New medications and new formulations have provided an increase in the cure rates for onychomycosis. Many cases of infection, however, are still not cured. It is not always obvious which factors are most relevant to reduction of cure, and factors may vary with each patient. For these reasons, a multitherapy approach to onychomycosis may be needed to individualize treatment to each patient's specific condition. Different presentations and severity levels of onychomycosis may respond differently to treatment modalities and require varying amounts of intervention. Nail débridement may be used to lessen the burden of infection in cases in which drug penetration may not occur adequately otherwise, such as dermatophytoma, onycholysis, or lateral infection. Ciclopirox nail lacquer has been approved for use in conjunction with regular débridement and represents the first approved multitherapy approach. Topical antifungals may be combined with oral antifungals to provide dual fronts of drug penetration. Similarly, two oral medications may be combined to provide a wider spectrum of antifungal activity and differential mode of action against the organisms, which may increase fungistatic or fungicidal action. There is a nonclinical component of therapy, represented by patient education on onychomycosis infection and treatment, which should be used to ensure that patient expectations are realistic and to encourage patient compliance with the chosen regimens.